Paroxetine Does Not Affect the Cardiac Safety and Pharmacokinetics of Terfenadine in Healthy Adult Men
| Autor: | Daniel Everitt, Rickey C. Etheredge, Diane K. Jorkasky, David E. Martin, Zussman Barry D, Lisa J. Benincosa |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Male medicine.medical_specialty Metabolic Clearance Rate Pharmacology QT interval Electrocardiography Pharmacokinetics Internal medicine medicine Humans Drug Interactions Pharmacology (medical) Terfenadine Cross-Over Studies CYP3A4 Chemistry Headache Area under the curve Heart Paroxetine Crossover study Psychiatry and Mental health Endocrinology Area Under Curve Pharmacodynamics Histamine H1 Antagonists Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Journal of Clinical Psychopharmacology. 17:451-459 |
| ISSN: | 0271-0749 |
| DOI: | 10.1097/00004714-199712000-00003 |
| Popis: | Potent CYP3A4 inhibitors such as ketoconazole can cause dangerous increases in plasma concentrations of the H-1 antagonist terfenadine. In light of recent reports that the selective serotonin re-uptake inhibitor antidepressants may be weak CYP3A4 inhibitors, this study was designed to investigate the effects of paroxetine on the pharmacodynamic and pharmacokinetic profile of terfenadine. Twelve healthy male volunteers participated in a randomized open-label, two-period, steady-state crossover study. Terfenadine (60 mg twice daily for 8 days) was administered alone and with paroxetine at steady state (20 mg once daily for 15 days, with terfenadine on days 8 through 15). Extensive electrocardiogram monitoring was conducted throughout, and terfenadine and carboxyterfenadine pharmacokinetics were assessed at the end of each treatment period. One subject withdrew because of adverse experiences related to paroxetine, but the other 11 subjects completed the study uneventfully. On the final day of coadministration, the rate-corrected QT interval (QT c ) was unaltered compared with terfenadine dosed alone; maximum QT c values (mean [SEMI) were 404 (4) and 405 (5) msec, respectively. Terfenadine pharmacokinetics were also unchanged; geometric mean steady-state area under the curve (AUC)T values were 30.0 ng.hr/mL during coadministration compared with 30.8 ng.hr/mL when dosed alone (p > 0.05). The corresponding C max values were 3.68 and 3.64 ng/mL (p > 0.05). There was, however, a small (on average 17-20%), unexplained reduction in the steady-state C max and AUCT of carboxyterfenadine during coadministration with paroxetine. In conclusion, paroxetine does not affect the pharmacokinetics or cardiovascular effects of terfenadine. The small reduction in carboxyterfenadine plasma concentrations is unlikely to be important clinically. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|